Lyophilization system and method

Abstract

System and method for lyophilization or freeze-drying is provided. During the freezing step, the material or solution to be frozen is initially brought to a temperature near or below its freezing temperature after which the pressure in the freeze-dryer chamber is reduced to induce nucleation of the material.

The invention claimed is: 
     
       1. A method of lyophilizing a material comprising the steps of:
 pressurizing the atmosphere within a chamber above atmospheric pressure and cooling the material in the pressurized chamber at a prescribed cooling rate to a desired nucleation temperature; 
 rapidly decreasing the pressure in the chamber to uniformly induce nucleation of freezing in the material at the desired nucleation temperature; 
 further cooling the nucleated material to or below a final temperature to freeze the material; and 
 drying the frozen material to produce a dried product having reduced moisture or solvent. 
 
     
     
       2. The method of lyophilizing as set forth in  claim 1  wherein the step of cooling the material further comprises cooling the material to a desired nucleation temperature near or below a phase transition temperature. 
     
     
       3. The method of lyophilizing as set forth in  claim 1  wherein the step of cooling the material further comprises cooling the material to a metastable state. 
     
     
       4. The method of lyophilizing as set forth in  claim 1  wherein the step of rapidly decreasing the pressure is initiated when the material attains a desired nucleation temperature. 
     
     
       5. The method of lyophilizing as set forth in  claim 1  wherein the step of rapidly decreasing the pressure is initiated at a desired time after the desired nucleation temperature. 
     
     
       6. The method of lyophilizing as set forth in  claim 1  wherein the material is selected from the group consisting of: a biopharmaceutical material, a pharmaceutical material, a chemical material, a biological material, a foodstuff or combinations thereof. 
     
     
       7. The method of lyophilizing as set forth in  claim 1  wherein the atmosphere within the pressurized chamber comprises a gas selected from the group consisting of: argon, nitrogen, helium, air, water vapor, oxygen, carbon dioxide, neon, xenon, krypton, hydrogen, or mixtures thereof. 
     
     
       8. The method of lyophilizing as set forth in  claim 1  wherein the pressurized atmosphere is below 25 psi above ambient pressure. 
     
     
       9. The method of lyophilizing as set forth in  claim 1  wherein the material is cooled to a temperature ranging from the phase transition temperature to about 20° C. below the phase transition temperature prior to the step of rapid depressurization. 
     
     
       10. The method of lyophilizing as set forth in  claim 1  wherein the material is cooled to a temperature ranging from the phase transition temperature to about 5° C. below the phase transition temperature prior to the step of rapid depressurization. 
     
     
       11. The method of lyophilizing as set forth in  claim 1  wherein the pressure is rapidly decreased by about 14 psi or more. 
     
     
       12. The method of lyophilizing as set forth in  claim 1  wherein the pressure is rapidly decreased by about 7 psi or more. 
     
     
       13. The method of lyophilizing as set forth in  claim 1  wherein the pressure is rapidly decreased such that an absolute pressure ratio, P i /P f , is about 1.2 or greater. 
     
     
       14. The method of lyophilizing as set forth in  claim 1  wherein the pressure is rapidly decreased at a pressure rate drop, ΔP/Δt, greater than about 0.2 psi per second. 
     
     
       15. The method of lyophilizing as set forth in  claim 1  wherein the pressure is rapidly decreased in 40 seconds or less. 
     
     
       16. The method of  claim 1  wherein the material further comprises one or more components selected from the group consisting of: live virus; attenuated virus; nucleic acids; monoclonal antibodies; polyclonal antibodies; proteins; peptides; or polypeptides. 
     
     
       17. The method of lyophilizing as set forth in  claim 1  wherein the material is held in a plurality of containers or vials and the dried product obtained from the plurality of containers or vials exhibit relatively uniform reconstitution time. 
     
     
       18. The method of lyophilizing as set forth in  claim 1  wherein the material is held in a plurality of containers or vials and the dried product obtained from the plurality of containers or vials exhibit relatively uniform residual moisture or solvent levels. 
     
     
       19. The method of  claim 1  wherein time required for drying the frozen material to reach a prescribed level of residual moisture is less than the time required for drying the frozen material that is stochastically nucleated to reach the prescribed level of residual moisture.